Drug addiction is a chronic disorder in which the individual consumes a drug persistently to the detriment of everyday physical and social functioning. The purpose of this Exploratory/Developmental Grant Application (R21) is to develop a nonhuman primate model of cocaine self-administration that incorporates the transition from low to high levels of drug taking, simulating features of the transition from initial to persistent drug use by people. Our primary hypothesis is that self-administration of cocaine escalates as a result of increased availability of the drug, and this escalation may reflect a use-dependent enhancement of the reinforcing effectiveness of cocaine. Our model will incorporate concepts of behavioral economic theory to evaluate changes in cocaine self-administration in rhesus monkeys under conditions of relatively restricted versus relatively unrestricted access to the drug. Specific Aim 1 will establish the degree to which cocaine self-administration escalates over time when access is increased from 1 hour/day to 6 hours/day. We will investigate the persistence of changes in cocaine self-administration by returning to the 1 hour/day access condition after a history of the 6 hour/day access condition. We also will determine the degree to which changes in cocaine self-administration are dependent on dose by establishing dose-response functions following exposure to the different access conditions. Specific Aim 2 will investigate the degree to which the reinforcing effects of cocaine are altered by changes in response requirements and by interposed periods of drug abstinence. We will test a range of response requirements to permit quantitative estimates of reinforcing effectiveness via behavioral economic analyses. By examining drug abstinence following exposure to increased access, we will determine if a drug-free period augments the reinforcing effects of cocaine in a manner similar to other abuse-related effects of cocaine (e.g., cue-induced relapse). In all experiments, within-session patterns of self-administration will be assessed to determine the extent to which cocaine taking switches from a relatively regulated to an unregulated pattern, possibly mirroring the loss of control observed in drug abusers. The results will provide needed information for developing a nonhuman primate model that can serve as a quantitative platform for future research on neuroadaptations underlying the transition to persistent cocaine self-administration. [unreadable] [unreadable]